This review will discuss generalized myxedema as it develops in hypothyroidism. First, the precipitating conditions (thyroprivic trophoprivic + goitrous forms) and the clinical manifestations of thyroid hormone deficiency are presented. Pathobiochemical and pathophysiological factors that lead to the main manifestations include retention of fluid, retention of sodium and hyponatremia. In particular are primary and direct consequences of reduced thyroid hormone levels, and secondary or indirect consequences, such as cardiovascular and renal derangements. In hypothyroidism many biochemical disturbances result. Most important is the interstitial deposition of hydrophilic mucopolysaccharides, which in turn lead to fluid and Na retention and impairment of blood circulation and lymphatic drainage. Myxedema, therefore, is to a large extent a lymphatic edema. Hyponatremia is an indirect consequence of the lack of T3 and is directly caused by impaired renal Na reabsorption. Renal Na,K-ATPase is reduced in specific segments. The often discussed role of inappropriate elevation of circulating ADH does not seem to be a key factor in myxedema. Impaired capacity of renal water excretion is caused by reduced GFR. We discuss the time dependent development of the derangement of different organ systems, and include recently published biochemical results, according to which the lack of T3 interferes not only with the metabolism of numerous compounds of the interstitial matrix, but also with cell surface proteins and intracellular proteins of microfilaments. Finally, we refer briefly to pretibial myxedema in states of hyperthyroidism, that is, infiltrative dermopathy in Graves' disease, which is caused by poorly understood autoimmune processes.